Human epidermal growth factor receptor 2 expression in mixed gastric carcinoma

Abstract

HER2 detection in mixed gastric carcinoma displays high heterogeneity. Relatively quantitative parameters are needed for assessing the level of HER2 amplification and protein expression.

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology

“…HER2-positive results by FISH were observed in 11% of cases with an IHC score of 0 and 12% of cases with an IHC score of 1þ. 3 Similarly, other studies 29,[74][75][76][77] have shown HER2 positivity by ISH in up to 14% to 24% of tumors with IHC scores of 0 or 1þ. These patients did not significantly benefit from the addition of trastuzumab to the chemotherapy regimen in the ToGA trial.…”

“…The concordance between IHC 3þ and ISH positivity was high, with 94% concordance in the ToGA trial and 62% to 100% in the literature, with most reporting concordance of 90% or higher. 3,8,29,[74][75][76][77][78] Since the benefit from the addition of HER2-directed therapy correlates with HER2 protein expression, initial HER2 testing should be performed by IHC. In situ hybridization should be reserved for IHC 2þ cases.…”

“…In situ hybridization should be reserved for IHC 2þ cases. In many studies, 8,29,74,76,77 ISH-positive results have been observed in 30% to 50% of IHC 2þ tumors. Of note, there can be interobserver variation in the interpretation of HER2 IHC, and the reproducibility of 1þ and 2þ scores can be low.…”

“…The rates of HER2 positivity vary for intestinal (3%-23.5%), diffuse (0%-6%), and mixed histology (0%-20%) cancers. 36,[85][86][87][88] Gastroesophageal adenocarcinoma has rare morphologic phenotypes that include adenosquamous, papillary, and neuroendocrine carcinomas, 74 but data regarding HER2 expression in such morphologic variants are limited. Most studies [8][9][10]57,86 have shown anatomic variation with HER2 expression/amplification being greater at the gastroesophageal junction than in the stomach (32.2% vs 21.4%).…”

HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies

“…A slight greater HER2 positivity incidence has been reported in EA (24%-35%), more frequently in the subgroup of intestinal-type, in comparison to GC (9.5%-21%) [68][69][70]. It is well known that the rate of HER2 overexpression is strictly related to GC histotype, showing higher frequency in the intestinal histotype (81.6%-91%) in comparison to the diffuse or mixed one (4%-7.9%) [71][72][73][74][75][76][77][78][79]. However, it has been reported an heterogenous pattern of HER2 immunoreactivity in intestinal GEA, exhibiting a combination of HER2-positive and HER2-negative regions [80][81][82][83][84].…”